"Computer Modelling in Barrett's Esophagus"
I intend to create a set of computer models of carcinogenesis and to use them to generate hypotheses that can be tested experimentally. These models will focus on the development of heterogeneous tumors and the role that crypt structured epithelium plays in the spread of neoplastic clones in Barrett's Esophagus. A model that can match the observed progression in Barrett's will not only help us understand the processes that govern the spread of neoplastic clones across healthy epithelial tissue, but it can also become a tool to facilitate diagnosis.
Clonal heterogeneity makes both the diagnosis and the treatment of tumors difficult. Treatment strategies might eliminate only certain neoplastic clones, giving the remaining ones a new opportunity for growth. Therefore, I am interested in creating a computer model that will generate realistic patterns of clones spreading across a simulated epithelial surface. I will calibrate the model using the Reid lab's biopsy data from Barrett's Esophagus patients. However, a simulation involving only epithelial sheet dynamics might be insufficient to match the observed data - the underlying crypt structures could play an essential role in the generation and spread of new clones. The spread of clones could be controlled by the processes of crypt bifurcation, wound healing, and epithelial restitution. Therefore, I expect to add these processes to the computer model. This modeling effort will complement current proposals at the FHCRC to investigate the clonal composition of crypts in Min mice and in biopsies from Barrett's patients.